Treatment of Recurrent Hepatitis C after Liver Transplantation

SUMMARY: Hepatitis C patients with advanced liver disease may benefit from interferon-based therapy before receiving a liver transplant, but side effects are common and response rates are low, according to a systematic research review described in the January 2011 issue of Alimentary Pharmacology and Therapeutics. Injected antibodies do not prevent the new liver from becoming infected, but pegyalted interferon plus ribavirin can cures recurring HCV about 30% of the time.

Over years or decades chronic hepatitis C virus (HCV) infection can progress to advanced liver disease including liver cancer and decompensated cirrhosis. Transplantation is the only option for end-stage liver failure, but HCV almost always infects the new donor liver soon thereafter and is a leading cause of graft and patient death.

P. Guillouche and C. Feray undertook a systematic review of research on treatment of hepatitis C before and after liver transplantation. They conducted a literature search for medical journals reports and national conference abstracts published between 1990 and 2010. They gave extra weight to randomized clinical trials, considered the "gold standard" of medical research.

Standard chronic hepatitis C therapy using pegylated interferon (Pegasys or PegIntron) plus ribavirin "must be considered before liver transplantation," the review authors wrote, since studies have shown that it reduces the risk of post-transplant HCV recurrence and disease progression. But studies show that treatment is "poorly tolerated" in general -- and even more so in people with advanced disease -- and produces poor results in patients with end-stage or hepatocellular carcinoma.

Clinicians have explored interferon-based therapy starting soon after liver transplantation in an attempt to prevent infection of the new graft, but have had only limited success. Unlike hepatitis B, administering anti-HCV antibodies does not reliably prevent recurrent infection.

Pegylated interferon plus ribavirin produces sustained virological response -- or continued undetectable HCV viral load 6 months after completing treatment -- in up to one-third of patients who experience HCV recurrence.

Based on these findings, the study authors concluded, "Currently available anti-viral therapy is effective only in a minority of transplanted patients infected with HCV."

New classes of directly-targeted antiviral drugs such as HCV protease and polymerase inhibitors -- the first of which are expected to be approved later this year -- may lead to better outcomes for this hard-to-treat population.

Investigator affiliation: Institut des Maladies de l'Appareil Digestif, Hôtel-Dieu, Nantes, France.

2/18/11

Reference
P Guillouche and C Feray. Systematic review: anti-viral therapy of recurrent hepatitis C after liver transplantation. Alimentary Pharmacology and Therapeutics 33(2):163-174 (Abstract). January 2011.